Patients and methods 460 patients with an average age of 64 years underwent 501 operations for non-spinal skeletal metastases. 7 % were operated for more than one metastasis. Carcinoma of the breast, prostate, kidney and lung were the dominating primary tumors.Results The survival rate was 0.4 at 1 year, 0.3 at 2 years and 0.2 at 3 years. Univariate analysis showed that survival was related to bone localization, skeletal metastatic load, presence of visceral metastases, Karnofsky performance score, primary tumor type, presence of a complete pathological fracture and preoperative hemoglobin content. Multivariate regression analysis showed that pathological fracture, visceral metastases, haemoglobin content < 7 mmol/L and lung cancer were negative prognostic factors for survival. Myeloma was the sole positive prognostic factor for survival.

The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p = 0.24 for PFS and 0.45 for OS, stratified by study).

Bilateral adrenocortical hyperplasia was present in 24 of 27 dogs with hyperadrenocorticalism. Two dogs had a unilateral adenoma, and one had a carcinoma of the adrenal cortex. Bilateral cortical hyperplasia was diffuse or nodular. The difference between the two patterns of hyperplasia was not associated with any consistent varation in the clinical or endocrinologic features. In the three dogs with adrenal cortical neoplasia there was marked cortical atrophy of the contralateral adrenal gland. Extracapsular nodular hyperplasia was common in the adrenals of dogs with hyperadrenocorticalism and also in older control dogs without endocrine disease. Ten of the dogs with bilateral adrenocortical hyperplasia were examined postmortem; two had a chromophobe adenoma of the pituitary, but no pituitary lesion was found in the others.

IntroductionPrevious studies have shown interference between EGFR TKI and chemotherapy in the cell cycle, thus reducing efficacy. In this RCT we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR mutated NSCLC.Materials and methodsTreatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy (E). The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and toxicity.ResultsBetween April 2014 to September 2016 twenty-two patients were randomized equally into both arms, the study was stopped due to slow accrual. Median follow up was 64 months. Median PFS was 13.7 months (95%CI 5.2–18.8) for CPE and 10.3 months (95%CI 7.1–15.5, HR 0.62 (95%CI 0.25–1.57)) for E, when compensating for number of days receiving erlotinib, PFS of CPE arm was superior (HR 0.24 (95% CI 0.07–0.83; p=0.02)). ORR was 64% for CPE versus 55% for E. Median OS was 31.7 months (95%CI 21.8–61.9) for CPE compared to 17.2 months (95%CI 11.5–45.5) for E (HR 0.58 (95%CI 0.22–1.41)). Patients treated with CPE had higher rates of treatment related fatigue, anorexia, weight loss and renal toxicity.ConclusionIntercalating erlotinib with cisplatin/pemetrexed provides a longer PFS compared to erlotinib alone in EGFR mutated NSCLC at the expense of more toxicity.

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